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<title>25 December, 2023</title>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Motorhomes as a Housing Alternative for the Indonesian Millennial Generation</strong> -
<div>
Motorhomes/campervans are a long-standing fad that is currently making a resurgence in all parts of the world. Because of the versatility of the motorhome, this lifestyle has grown in popularity, not only among hippies, but also among families who wish to have fun or live a nomadic (moving) existence, especially with the rapid rise of the Internet of Things. We can learn from the Covid-19 pandemic that work and study can be done anywhere, whether at home, in recreational spaces, in third rooms, and so on. Motorhomes can now be purchased at reasonable costs. Furthermore, the motorhome can be customized to meet your specific demands and functions. Motorhomes can be created from simple automobiles using any car foundation, such as an MPV, Van, SUV, Middle Size Bus, Full Size Bus, or even a sedan, rather than full size RVs with big proportions and luxurious equipment. The purpose of this study is to define the motorhome/campervan concept and its potential as an alternative housing type. Furthermore, the potential is fairly large for Indonesian millennials, who appear to have a lot of issues on housing ownership mostly because the affrodability (economic) aspect and also considering the raising on nomadic and flexible lifestyle. Motorhomes are an excellent option to economical housing since they are mobile, have flexible layouts, and provide a comfortable living space especially for Youth Indonesia’s Millenial who’s carving for a unique experience.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/x4zgq/" target="_blank">Motorhomes as a Housing Alternative for the Indonesian Millennial Generation</a>
</div></li>
<li><strong>CompHEAR: A Customizable and Scalable Web-Enabled Auditory Performance Evaluation Platform for Cochlear Implant Sound Processing Research</strong> -
<div>
Objective: Cochlear implants (CIs) are auditory prostheses for individuals with severe to profound hearing loss, offering substantial but incomplete restoration of hearing function by stimulating the auditory nerve using electrodes. However, progress in CI performance and innovation has been constrained by the inability to rapidly test multiple sound processing strategies. Current research interfaces provided by major CI manufacturers have limitations in supporting a wide range of auditory experiments due to portability, programming difficulties, and the lack of direct comparison between sound processing algorithms. To address these limitations, we present the CompHEAR research platform, designed specifically for the Cochlear Implant Hackathon, enabling researchers to conduct diverse auditory experiments on a large scale. Study Design: Quasi-experimental. Setting: Virtual. Methods: CompHEAR is an open-source, user-friendly platform which offers flexibility and ease of customization, allowing researchers to set up a broad set of auditory experiments. CompHEAR employs a vocoder to simulate novel sound coding strategies for CIs. It facilitates even distribution of listening tasks among participants and delivers real-time metrics for evaluation. The software architecture underlies the platform's flexibility in experimental design and its wide range of applications in sound processing research. Results: Performance testing of the CompHEAR platform ensured that it could support at least 10,000 concurrent users. The CompHEAR platform was successfully implemented during the COVID-19 pandemic and enabled global collaboration for the CI Hackathon (www.cihackathon.com). Conclusion: The CompHEAR platform is a useful research tool that permits comparing diverse signal processing strategies across a variety of auditory tasks with crowdsourced judging. Its versatility, scalability, and ease of use can enable further research with the goal of promoting advancements in cochlear implant performance and improved patient outcomes.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.22.573126v1" target="_blank">CompHEAR: A Customizable and Scalable Web-Enabled Auditory Performance Evaluation Platform for Cochlear Implant Sound Processing Research</a>
</div></li>
<li><strong>Long Covid Perspectives: history, paradigm shifts, global challenges</strong> -
<div>
The Covid-19 pandemic is one of the most devastating health disasters in recorded history. In addition to the significant death toll, the pandemic is leaving behind a long tail of prolonged disease and disability. The long-term symptoms, clinical signs and sequelae of SARS-CoV-2 infection are collectively known as Long Covid – a patient-made term that was created and gained consistency in just a few months in Spring to Summer 2020. Long Covid was openly recognized by the World Health Organization (WHO) in August 2020, following intense advocacy by Covid-19 survivors. Long Covid has been described as the first illness identified, named and defined by patients finding one other on social media such as Twitter. As a disease entity named and defined collectively by patients, Long Covid has the potential to change knowledge building in medicine, while centring patient expertise within the biomedical community. This paper will, first, explore the rise of Long Covid as patient-made term, clinical entity and collective, grassroots, international advocacy–research movement in early 2020 and beyond. This happened while people with Covid-19 suffered abandonment and lack of care in the pandemic’s disaster context. Second, I will discuss some key paradigm shifts triggered by this ground-breaking patient-driven, collective advocacy–research, while sketching links with earlier patient movements, such as around HIV/AIDS. Then, I will explore the role of Long Covid advocacy–research in our digital era. This advocacy took place during a pandemic when digital spaces such as Twitter and Facebook were often the only arenas available to Covid-19 survivors. Moreover, I will raise some pressing issues around epistemic injustice in relation to the use of patient-produced data and the recognition of patient contributions to knowledge. Finally, I will address the need to fully acknowledge the nature, scope, and severity of Long Covid, which are detailed in thousands of scientific publications, including in relation to the ongoing spread of SARS-CoV-2.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/u3bfy/" target="_blank">Long Covid Perspectives: history, paradigm shifts, global challenges</a>
</div></li>
<li><strong>Genomic analysis of Staphylococcus aureus isolates from bacteremia reveals genetic features associated with the COVID-19 pandemic</strong> -
<div>
Genomic analyses of bacterial isolates are necessary to monitor the prevalence of antibiotic resistance genes and virulence determinants. Herein, we provide a comprehensive genomic description of a collection of 339 Staphylococcus aureus strains isolated from patients with bacteremia between 2014 and 2022. Nosocomial acquisition accounted for 56.6% of episodes, with vascular catheters being the predominant source of infection (31.8%). Cases of fatality (27.4%), persistent bacteremia (19.5%) and diagnosis of septic emboli (24.2%) were documented. During the COVID-19 pandemic, we observed a 140% increase of the episodes of S. aureus bacteremia per year, with a concomitant increase of the cases from nosocomial origin. This prompted us to investigate the existence of genetic features associated with S. aureus isolates from the COVID-19 pandemic. While genes conferring resistance to {beta}-lactams (blaI-blaR-blaZ), macrolides (ermA, ermC, ermT, mphC, msrA) and aminoglycosides (ant(4')-Ia, ant(9)-Ia, aph(3')-IIIa, aph(2'')-Ih) were prevalent in our collection, detection of the msrA and mphC genes increased significantly in pandemic S. aureus isolates. Similarly, we observed a higher prevalence of isolates carrying the genes encoding the Clumping Factors A and B, involved in fibrinogen binding. Of note, macrolides were extensively used as accessory therapy for COVID-19 and fibrinogen levels were usually elevated upon SARS-CoV-2 infection. Therefore, our results reveal a remarkable adaptation of the S. aureus isolates to the COVID-19 pandemic context and demonstrates the potential of whole-genome sequencing to conduct molecular epidemiology studies.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.22.572975v1" target="_blank">Genomic analysis of Staphylococcus aureus isolates from bacteremia reveals genetic features associated with the COVID-19 pandemic</a>
</div></li>
<li><strong>Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants</strong> -
<div>
The evolution of SARS-CoV-2 variants with increased fitness has been accompanied by structural changes in the spike (S) proteins that are the major target for the adaptive immune response. Single-particle cryo-EM analysis of soluble S from SARS-CoV-2 variants has revealed this structural adaptation at high-resolution. The analysis of S trimers in situ on intact virions has the potential to provide more functionally relevant insights into S structure and virion morphology. Here, we characterized B.1, Alpha, Beta, Gamma, Delta, Kappa, and Mu variants by cryo-electron microscopy and tomography, assessing S cleavage, virion morphology, S incorporation, "in-situ" high-resolution S structures and the range of S conformational states. We found no evidence for adaptive changes in virion morphology, but describe multiple different positions in the S protein where amino acid changes alter local protein structure. Considered together, our data is consistent with a model where amino acid changes at multiple positions from the top to the base of the spike cause structural changes that can modulate the conformational dynamics of S.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.21.572824v1" target="_blank">Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants</a>
</div></li>
<li><strong>The SARS-CoV-2 infection (COVID-19) era impact on incidence of sudden deaths due to Myocardial Infarction (Heart Attack) in States and Union Territories of India- A cross-sectional comparative study (2018-2022)</strong> -
<div>
Background-COVID-19 pandemic increased the risk of CVD (cardiovascular disease). There is lack of comparative assessment on the incidence of sudden death due to MI during and before COVID-19. This study aimed to quantify this assessment. Another quest to start this study is that several studies have reported COVID-19 vaccine-associated myocarditis/cardiomyopathy. Methods and results-This study was based on NCRB data from all states and UTs of India who died suddenly due to MI between 1 January 2018 and 31 December 2022. 5 coastal states of India accounts for about 70 % of all MI cases related sudden death. The base year 2018 is having least whereas the last year 2022 is having the largest number of total new MI cases related mortality detected in one individual year. The largest and noteworthy percent change in sudden death due to MI in males is found in 2022 when it increased by 14.26% (is it due to delayed cardiomyopathy due to COVID-19 or its due to Vaccine? This will be a matter of research in coming era). This study revealed that there is 25.80 percent increase in total number of new MI cases related mortality in 2022 in comparison to pre-COVID-19 year of 2018. There is an overall increase of 11.24 percent in sudden death due to MI cases in males during the COVID-19 period. The Male-Sudden death due to Myocardial Infarction increased during COVID-19 year 2022 by 26.71 percent in comparison to 2018 pre- COVID-19 year. Conclusion-Sudden death due to MI increased during COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/dcr9a/" target="_blank">The SARS-CoV-2 infection (COVID-19) era impact on incidence of sudden deaths due to Myocardial Infarction (Heart Attack) in States and Union Territories of India- A cross-sectional comparative study (2018-2022)</a>
</div></li>
<li><strong>MixOmics Integration of Biological Datasets Identifies Highly Correlated Key Variables of COVID-19 severity.</strong> -
<div>
BackgroundDespite several years since the COVID-19 pandemic was declared, challenges remain in understanding the factors that can predict the severity of COVID-19 disease and complications of SARS-CoV-2 infection. While many large-scale Multiomic datasets have been published, integration of these datasets has the potential to substantially increase the biological insight gained allowing a more complex comprehension of the disease pathogenesis. Such insight may improve our ability to predict disease progression, detect severe cases more rapidly and develop effective therapeutics. MethodsIn this study we have applied an innovative machine learning algorithm to delineate COVID-severity based on integration of paired samples of proteomic and transcriptomic data from a small cohort of patients testing positive for SARS-CoV-2 infection with differential disease severity. Targeted plasma proteomics and an onco-immune targeted transcriptomic panel was performed on sequential samples from a cohort of 23 severe, 21 moderate and 10 mild COVID-19 patients. We applied DIABLO, a new integrative method, to identify multi- omics biomarker panels that can discriminate between multiple phenotypic groups, such as the varied severity of disease in COVID-19 patients. ResultsAs COVID-19 severity is known among our sample group, we can train models using this as the outcome variable and calculate features that are important predictors of severe disease. In this study, we detect highly correlated key variables of severe COVID-19 using transcriptomic discriminant analysis and multi-omics integration methods. ConclusionsThis approach highlights the power of data integration from a small cohort of patients offering a better biological understanding of the molecular mechanisms driving COVID-19 severity and an opportunity to improve prediction of disease trajectories and targeted therapeutics.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.14.557558v2" target="_blank">MixOmics Integration of Biological Datasets Identifies Highly Correlated Key Variables of COVID-19 severity.</a>
</div></li>
<li><strong>Tracking SARS-CoV-2 variants of concern in wastewater: an assessment of nine computational tools using simulated genomic data</strong> -
<div>
Wastewater-based surveillance (WBS) is an important epidemiological and public health tool for tracking pathogens across the scale of a building, neighbourhood, city, or region. WBS gained widespread adoption globally during the SARS-CoV-2 pandemic for estimating community infection levels by qPCR. Sequencing pathogen genes or genomes from wastewater adds information about pathogen genetic diversity which can be used to identify viral lineages (including variants of concern) that are circulating in a local population. Capturing the genetic diversity by WBS sequencing is not trivial, as wastewater samples often contain a diverse mixture of viral lineages with real mutations and sequencing errors, which must be deconvoluted computationally from short sequencing reads. In this study we assess nine different computational tools that have recently been developed to address this challenge. We simulated 100 wastewater sequence samples consisting of SARS-CoV-2 BA.1, BA.2, and Delta lineages, in various mixtures, as well as a Delta-Omicron recombinant and a synthetic novel lineage. Most tools performed well in identifying the true lineages present and estimating their relative abundances, and were generally robust to variation in sequencing depth and read length. While many tools identified lineages present down to 1% frequency, results were more reliable above a 5% threshold. The presence of an unknown synthetic lineage, which represents an unclassified SARS-CoV-2 lineage, increases the error in relative abundance estimates of other lineages, but the magnitude of this effect was small for most tools. The tools also varied in how they labelled novel synthetic lineages and recombinants. While our simulated dataset represents just one of many possible use cases for these methods, we hope it helps users understand potential sources of noise or bias in wastewater sequencing data and to appreciate the commonalities and differences across methods.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.20.572426v1" target="_blank">Tracking SARS-CoV-2 variants of concern in wastewater: an assessment of nine computational tools using simulated genomic data</a>
</div></li>
<li><strong>Deciphering Abnormal Platelet Subpopulations in Inflammatory Diseases through Machine Learning and Single-Cell Transcriptomics</strong> -
<div>
Introduction: The transcriptional heterogeneity of activated platelets, play a significant role in contributing to negative outcomes in sepsis, COVID-19, and autoimmune diseases such as systemic lupus erythematosus (SLE). Despite this, our understanding of these heterogeneous platelet responses remains limited. In this study, we aim to investigate the diverse transcriptional profiles of activated platelets in these diseases, with the goal of deciphering this platelet heterogeneity for new therapeutic strategies to target abnormal and pathogenic platelet subtypes. Materials and methods: We obtained the single cell transcriptional profiles of blood platelets from patients with COVID-19, sepsis, and SLE. Utilizing machine learning algorithms, Deep Neural Network (DNN) and eXtreme Gradient Boosting (XGB), we discerned the distinct transcriptomic signatures indicative of fatal versus survival clinical outcomes. Our methodological framework incorporated source data annotations and platelet markers and used SingleR and Seurat for detailed profiling. Additionally, we implemented Uniform Manifold Approximation and Projection (UMAP) for dimensionality reduction and visualization, aiding in the detection of various platelet subtypes and their correlation with disease status and patient outcomes. Results: Our study identified distinct platelet subpopulations that are associated with disease severity. We demonstrated that alterations in platelet transcription patterns can exacerbate endotheliopathy, potentially heightening the risk of coagulation in fatal patients. Moreover, these changes can also influence lymphocyte function, indicating a more extensive role for platelets in inflammatory and immune responses. Conclusions: Enhanced transcriptional heterogeneity in activated platelets is linked to adverse outcomes in conditions such as sepsis, COVID-19, and autoimmune diseases. The discovery of these unique platelet subpopulations paves the way for innovative therapeutic strategies targeting platelet activation, which could potentially improve patient outcomes.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.20.572680v1" target="_blank">Deciphering Abnormal Platelet Subpopulations in Inflammatory Diseases through Machine Learning and Single-Cell Transcriptomics</a>
</div></li>
<li><strong>Persistence of an infectious form of SARS-CoV-2 post protease inhibitor treatment of permissive cells in vitro</strong> -
<div>
Reports have described SARS-CoV-2 rebound in COVID-19 patients treated with nirmatrelvir, a 3CL protease inhibitor. The cause remains a mystery, although drug resistance, re-infection, and lack of adequate immune responses have been excluded. We now present virologic findings that provide a clue to the cause of viral rebound, which occurs in ~20% of the treated cases. The persistence of an intermediary form of infectious SARS-CoV-2 was experimentally documented in vitro after treatment with nirmatrelvir or another 3CL protease inhibitor, but not with a polymerase inhibitor, remdesivir. This infectious intermediate decayed slowly with a half-life of ~1 day, suggesting that its persistence could outlive the treatment course to re-ignited SARS-CoV-2 infection as the drug is eliminated. Additional studies are needed to define the nature of this viral intermediate, but our findings point to a particular direction for future investigation and offer a specific treatment recommendation that should be tested clinically.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.20.572655v1" target="_blank">Persistence of an infectious form of SARS-CoV-2 post protease inhibitor treatment of permissive cells in vitro</a>
</div></li>
<li><strong>Humoral immune responses to the monovalent XBB.1.5-adapted BNT162b2 mRNA booster</strong> -
<div>
Continued SARS-CoV-2 evolution and immune escape necessitated the development of updated vaccines, and a monovalent vaccine incorporating the XBB.1.5 variant spike protein is currently being rolled out. Amidst the emergence of the highly mutated BA.2.86 lineage and against the backdrop of pronounced immune imprinting, it is important to characterize the antibody responses following vaccination, particularly in the elderly. Here, we show that the monovalent XBB.1.5-adapted booster vaccination substantially enhanced both binding and neutralising antibody responses against a panel of variants, including BA.2.86, in an older population with four or more previous vaccine doses. Furthermore, neutralizing antibody titers to XBB.1.5 and BA.2.86 were boosted more strongly than titers to historical variants were. Our findings thereby suggest increased vaccine induced protection against both antigenically matched variants, as well as the more distant BA.2.86 variant, and support current vaccine policies recommending a monovalent XBB.1.5 booster dose to older individuals.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.21.572575v1" target="_blank">Humoral immune responses to the monovalent XBB.1.5-adapted BNT162b2 mRNA booster</a>
</div></li>
<li><strong>Appraising the decision-making process concerning COVID-19 policy in postsecondary education in Canada: A critical scoping review protocol</strong> -
<div>
Responses to COVID-19 in Canadian postsecondary education have overhauled usual norms and practices, with policies of unclear rationale implemented under the pressure of a public health emergency. However, despite the unprecedented nature of these policies and their dramatic impact on millions of lives, the decision-making process leading to them has not been documented or appraised. Drawing from macro and micro theories of public policy, specifically the critical tradition in policy studies exemplified by Carol Bacchi’s approach “What is the problem represented to be” (WPR), we will conduct a scoping review of COVID-19 policies in Canadian postsecondary education, guided by Arksey and O’Malley’s framework for scoping reviews and by the team-based approach of Levan and colleagues. Data will include diverse and publicly available documents to capture multiple stakeholders’ perspectives on the phenomenon of interest, and will be retrieved from university, newsletter, and legal websites through combinations of search terms adapted to specific data types. Two reviewers will independently screen, chart, analyse and synthesize the data and disagreements will be resolved through full team discussion. By identifying, summarizing, and appraising the evidence, our review should inform practices that can contribute to effective and equitable public health policies in postsecondary institutions moving forward.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/u3e28/" target="_blank">Appraising the decision-making process concerning COVID-19 policy in postsecondary education in Canada: A critical scoping review protocol</a>
</div></li>
<li><strong>Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating</strong> -
<div>
The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid-interface (ALI) were used to model upper-respiratory infection and human lung epithelial cell lines used to model lower-respiratory infection. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency. In primary nasal cultures, Omicron replicated to the highest titers at early time points, followed by Delta, paralleling comparative studies of population sampling. All SARS-CoV-2 viruses entered the cell primarily via a transmembrane serine protease 2 (TMPRSS2)-dependent pathway, and Omicron was more likely to use an endosomal route of entry. All VOCs activated and overcame dsRNA-induced cellular responses including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation and protein kinase R activation. Among the VOCs, Omicron infection induced expression of the most IFN and IFN stimulated genes. Infections in nasal cultures resulted in cellular damage, including a compromise of cell-barrier integrity and loss of nasal cilia and ciliary beating function, especially during Delta infection. Overall, Omicron was optimized for replication in the upper-respiratory system and least-favorable in the lower-respiratory cell line; and Delta was the most cytopathic for both upper and lower respiratory cells. Our findings highlight the functional differences among VOCs at the cellular level and imply distinct mechanisms of pathogenesis in infected individuals.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.24.553565v2" target="_blank">Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating</a>
</div></li>
<li><strong>Integrated histopathology, spatial and single cell transcriptomics resolve cellular drivers of early and late alveolar damage in COVID-19</strong> -
<div>
The most common cause of death due to COVID-19 remains respiratory failure. Yet, our understanding of the precise cellular and molecular changes underlying lung alveolar damage is limited. Here, we integrate single cell transcriptomic data of COVID-19 donor lungs with spatial transcriptomic data stratifying histopathological stages of diffuse alveolar damage (DAD). We identify changes in cellular composition across progressive DAD, including waves of molecularly distinct macrophages and depleted epithelial and endothelial populations throughout different types of tissue damage. Predicted markers of pathological states identify immunoregulatory signatures, including IFN-alpha and metallothionein signatures in early DAD, and fibrosis-related collagens in organised DAD. Furthermore, we predict a fibrinolytic shutdown via endothelial upregulation of SERPINE1/PAI-1. Cell-cell interaction analysis revealed macrophage-derived SPP1/osteopontin signalling as a key regulator during early DAD. These results provide the first comprehensive, spatially resolved atlas of DAD stages, highlighting the cellular mechanisms underlying pro-inflammatory and pro-fibrotic pathways across alveolar damage progression.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.20.572494v1" target="_blank">Integrated histopathology, spatial and single cell transcriptomics resolve cellular drivers of early and late alveolar damage in COVID-19</a>
</div></li>
<li><strong>Deep profiling of antigen-specific B cells from different pathogens identifies novel compartments in the IgG memory B cell and antibody-secreting cell lineages</strong> -
<div>
A better understanding of the bifurcation of human B cell differentiation into memory B cells (MBC) and antibody-secreting cells (ASC) and identification of MBC and ASC precursors is crucial to optimize vaccination strategies or block undesired antibody responses. To unravel the dynamics of antigen-induced B cell responses, we compared circulating B cells reactive to SARS-CoV-2 (Spike, RBD and Nucleocapsid) in COVID-19 convalescent individuals to B cells specific to Influenza-HA, RSV-F and TT, induced much longer ago. High-dimensional spectral flow cytometry indicated that the decision point between ASC- and MBC-formation lies in the CD43+CD71+IgG+ Activated B cell compartment, showing properties indicative of recent germinal center activity and recent antigen encounter. Within this Activated B cells compartment, CD86+ B cells exhibited close phenotypical similarity with ASC, while CD86- B cells were closely related to IgG+ MBCs. Additionally, different activation stages of the IgG+ MBC compartment could be further elucidated. The expression of CD73 and CD24, regulators of survival and cellular metabolic quiescence, discerned activated MBCs from resting MBCs. Activated MBCs (CD73- CD24lo) exhibited phenotypical similarities with CD86- IgG+ Activated B cells and were restricted to SARS-CoV-2 specificities, contrasting with the resting MBC compartment (CD73-/CD24hi) that exclusively encompassed antigen-specific B cells established long ago. Overall, these findings identify novel stages for IgG+ MBC and ASC formation and bring us closer in defining the decision point for MBC or ASC differentiation.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.19.572339v1" target="_blank">Deep profiling of antigen-specific B cells from different pathogens identifies novel compartments in the IgG memory B cell and antibody-secreting cell lineages</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Combined Modified RNA Vaccine Candidate Against COVID-19 and Influenza.</strong> - <b>Conditions</b>: Influenza; COVID-19 <br/><b>Interventions</b>: Biological: Influenza and COVID-19 Combination A; Biological: Licensed influenza vaccine; Biological: COVID-19 Vaccine; Biological: Influenza and COVID-19 Combination B; Biological: Placebo <br/><b>Sponsors</b>: BioNTech SE; Pfizer <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Transcranial Pulse Stimulation (TPS) in Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Fatigue <br/><b>Interventions</b>: Device: Transcranial pulse stimulation Verum; Device: Transcranial pulse stimulation Sham <br/><b>Sponsors</b>: Medical University of Vienna; Campus Bio-Medico University <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluate the Efficacy and Safety of “Formosa 1-Breath Free (NRICM101)” in Subjects With the Symptoms of COVID-19 or Influenza-like Disease</strong> - <b>Conditions</b>: Influenza Viral Infections; COVID-19 <br/><b>Interventions</b>: Drug: Formosa 1-Breath Free (NRICM101); Drug: Placebo control drug <br/><b>Sponsors</b>: China Medical University Hospital; Tian-I Pharmaceutical,. Co. Ltd.; China Medical University, China; Qualitix Clinical Research Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 3 Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of Booster Vaccination With Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell); Biological: Recombinant COVID-19 Variant Vaccine (Sf9 Cell); Biological: Placebo <br/><b>Sponsors</b>: WestVac Biopharma Co., Ltd.; WestVac Biopharma (Guangzhou) Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Restoring Energy With Sub-symptom Threshold Optimized Rehabilitation Exercise for Long COVID</strong> - <b>Conditions</b>: Long Covid19; Exercise Intolerance, Riboflavin-Responsive <br/><b>Interventions</b>: Behavioral: Restoring Energy with Sub-symptom Threshold Aerobic Rehabilitation Exercise; Behavioral: Light Stretching/Breathing Exercises <br/><b>Sponsors</b>: Columbia University; New York University <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Pilot Study of Liraglutide (A Weight Loss Drug) in High Risk Obese Participants With Cognitive and Memory Issues</strong> - <b>Conditions</b>: Multiple Sclerosis; Long COVID; Long Covid19; Obese; Obesity; Obesity, Morbid; Acute Leukemia in Remission <br/><b>Interventions</b>: Drug: Liraglutide Pen Injector [Saxenda]; Other: Medication Diary <br/><b>Sponsors</b>: University of Chicago <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>EXERCISE TRAINING USING AN APP ON PHYSICAL CARDIOVASCULAR FUNCTION INDIVIDUALS WITH POST-COVID-19 SYNDROME</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Exercise; Behavioral: Control <br/><b>Sponsors</b>: University of Nove de Julho <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 1 Trial of Recombinant COVID-19 Trivalent Protein Vaccine （CHO Cell）LYB002V14 in Booster Vaccination</strong> - <b>Conditions</b>: SARS-CoV-2; COVID-19 Vaccine <br/><b>Interventions</b>: Biological: 30μg dose of LYB002V14; Biological: 60μg dose of LYB002V14; Biological: placebo <br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Vaccine Effectiveness Against Recurrent Infection Among Lung Cancer Patients and Biomarker Research</strong> - <b>Conditions</b>: COVID-19 Recurrent; Lung Cancer; Vaccination; Antibody; Chemotherapy; Immune Checkpoint Inhibitor <br/><b>Interventions</b>: Biological: Any Chinese government-recommended COVID-19 booster vaccine <br/><b>Sponsors</b>: Peking Union Medical College Hospital <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IMMUNERECOV CONTRIBUTES TO IMPROVEMENT OF RESPIRATORY AND IMMUNOLOGICAL RESPONSE IN POST-COVID-19 PATIENTS.</strong> - <b>Conditions</b>: Long Covid19; Dietary Supplements; Respiratory Tract Infections; Inflammation <br/><b>Interventions</b>: Dietary Supplement: Nutritional blend (ImmuneRecov). <br/><b>Sponsors</b>: Federal University of São Paulo <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Physical Activity Coaching in Patients With Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Self-monitoring; Behavioral: Goal setting and review; Behavioral: Education; Behavioral: Feedback; Behavioral: Contact; Behavioral: Exercise; Behavioral: Report; Behavioral: Social support; Behavioral: Group activities; Behavioral: World Health Organization recommendations for being physically active <br/><b>Sponsors</b>: University of Alcala; Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on Post-Acute COVID-19 Syndrome in Improvement of COVID-19 Rehabilitated Patients by Respiratory Training</strong> - <b>Conditions</b>: COVID-19, Post-Acute COVID-19 Syndrome, Dyspnea, Incentive Spirometer <br/><b>Interventions</b>: Device: breathing training <br/><b>Sponsors</b>: Tri-Service General Hospital <br/><b>Active, not recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Does denosumab exert a protective effect against COVID-19? Results of a large cohort study</strong> - CONCLUSION: Our study confirms that denosumab may be safely continued in COVID-19 patients. RANK/RANKL inhibition seems associated with a reduced incidence of symptomatic COVID-19, particularly among the elderly.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Intranasal murine pneumonia virus-vectored SARS-CoV-2 vaccine induces mucosal and serum antibodies in macaques</strong> - Next-generation SARS-CoV-2 vaccines are needed that induce systemic and mucosal immunity. Murine pneumonia virus (MPV), a murine homolog of respiratory syncytial virus, is attenuated by host-range restriction in nonhuman primates and has a tropism for the respiratory tract. We generated MPV vectors expressing the wild-type SARS-CoV-2 spike protein (MPV/S) or its prefusion-stabilized form (MPV/S-2P). Both vectors replicated similarly in cell culture and stably expressed S. However, only S-2P was…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacies of S-nitrosoglutathione (GSNO) and GSNO reductase inhibitor in SARS-CoV-2 spike protein induced acute lung disease in mice</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially surfaced in late 2019, often triggers severe pulmonary complications, encompassing various disease mechanisms such as intense lung inflammation, vascular dysfunction, and pulmonary embolism. Currently, however, there’s no drug addressing all these mechanisms simultaneously. This study explored the multi-targeting potential of S-nitrosoglutathione (GSNO) and N6022, an inhibitor of GSNO reductase (GSNOR) on markers…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comparative transcriptome analysis of SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-229E identifying potential IFN/ISGs targets for inhibiting virus replication</strong> - INTRODUCTION: Since its outbreak in December 2019, SARS-CoV-2 has spread rapidly across the world, posing significant threats and challenges to global public health. SARS-CoV-2, together with SARS-CoV and MERS-CoV, is a highly pathogenic coronavirus that contributes to fatal pneumonia. Understanding the similarities and differences at the transcriptome level between SARS-CoV-2, SARS-CoV, as well as MERS-CoV is critical for developing effective strategies against these viruses.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity</strong> - The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting the tissue factor coagulation initiation complex prevents antiphospholipid antibody development</strong> - Antiphospholipid antibodies (aPL) in primary or secondary antiphospholipid syndrome (APS) are a major cause for acquired thrombophilia, but specific interventions preventing autoimmune aPL development are an unmet clinical need. While autoimmune aPL cross-react with various coagulation regulatory proteins, lipid-reactive and COVID-19 patient-derived aPL recognize the endo-lysosomal phospholipid lysobisphosphatidic acid (LBPA) presented by the cell surface expressed endothelial protein C receptor…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Tissue factor binds to and inhibits interferon-α receptor 1 signaling</strong> - Tissue factor (TF), which is a member of the cytokine receptor family, promotes coagulation and coagulation-dependent inflammation. TF also exerts protective effects through unknown mechanisms. Here, we showed that TF bound to interferon-α receptor 1 (IFNAR1) and antagonized its signaling, preventing spontaneous sterile inflammation and maintaining immune homeostasis. Structural modeling and direct binding studies revealed binding of the TF C-terminal fibronectin III domain to IFNAR1, which…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Avian coronavirus infectious bronchitis virus Beaudette strain NSP9 interacts with STAT1 and inhibits its phosphorylation to facilitate viral replication</strong> - Avian coronavirus, known as infectious bronchitis virus (IBV), is the causative agent of infectious bronchitis (IB). Viral nonstructural proteins play important roles in viral replication and immune modulation. IBV NSP9 is a component of the RNA replication complex for viral replication. In this study, we uncovered a function of NSP9 in immune regulation. First, the host proteins that interacted with NSP9 were screened. The immune-related protein signal transducer and activator of transcription…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cholesterol depletion inhibits rabies virus infection by restricting viral adsorption and fusion</strong> - Rabies is an ancient zoonotic disease caused by the rabies virus (RABV), and a sharp increase in rabies cases and deaths were observed following the COVID-19 pandemic, indicating that it still poses a severe public health threat in most countries in the world. Cholesterol is one of the major lipid components in cells, and the exact role of cholesterol in RABV infection remains unclear. In this study, we initially observed that cellular cholesterol levels were significantly elevated in RABV…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical utility of quantitative immunoassays and surrogate virus neutralization tests for predicting neutralizing activity against the SARS-CoV-2 Omicron BA.1 and BA.5 variants</strong> - Developing new antibody assays for emerging SARS-CoV-2 variants is challenging. SARS-CoV-2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT-positive sera, we noticed that log-transformed optical density (OD) ratio of wild-type (WT) sVNT exhibited better titer-correlation with plaque reduction neutralization test (PRNT) than % inhibition…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Antiviral Activity of the Lectin Griffithsin against SARS-CoV-2 Is Enhanced by the Presence of Structural Proteins</strong> - Although COVID-19 transmission has been reduced by the advent of vaccinations and a variety of rapid monitoring techniques, the SARS-CoV-2 virus itself has shown a remarkable ability to mutate and persist. With this long track record of immune escape, researchers are still exploring prophylactic treatments to curtail future SARS-CoV-2 variants. Specifically, much focus has been placed on the antiviral lectin Griffithsin in preventing spike protein-mediated infection via the hACE2 receptor…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cholesterol 25-Hydroxylase Suppresses Swine Acute Diarrhea Syndrome Coronavirus Infection by Blocking Spike Protein-Mediated Membrane Fusion</strong> - Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an emerging porcine intestinal coronavirus that can cause acute diarrhea, vomiting, rapid weight loss, and high mortality in newborn piglets. Cholesterol 25-hydroxylase (CH25H) is a molecular mediator of innate antiviral immunity and converts cholesterol to 25-hydroxycholesterol (25HC). Previous studies have reported that CH25H and 25HC have an antiviral effect against multiple viruses. However, the interplay between SADS-CoV infection and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Tetherin Restricts SARS-CoV-2 despite the Presence of Multiple Viral Antagonists</strong> - Coronavirus infection induces interferon-stimulated genes, one of which encodes Tetherin, a transmembrane protein inhibiting the release of various enveloped viruses from infected cells. Previous studies revealed that SARS-CoV encodes two Tetherin antagonists: the Spike protein (S), inducing lysosomal degradation of Tetherin, and ORF7a, altering its glycosylation. Similarly, SARS-CoV-2 has also been shown to use ORF7a and Spike to enhance virion release in the presence of Tetherin. Here, we…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Functional Implications of Broad Spectrum Bioactive Compounds Targeting RNA-Dependent RNA Polymerase (RdRp) in the Context of the COVID-19 Pandemic</strong> - CONCLUSIONS: Future risk mitigation and treatment strategies against forthcoming SARS-CoV-2 variants should consider targeting RdRp proteins instead of surface proteins.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation</strong> - Severe COVID-19 patients exhibit impaired IFN-I response due to decreased IFN-β production, allowing persistent viral load and exacerbated inflammation. While the SARS-CoV-2 nucleocapsid (N) protein has been implicated in inhibiting innate immunity by interfering with IFN-β signaling, the specific underlying mechanism still needs further investigation for a comprehensive understanding. This study reveals that the SARS-CoV-2 N protein enhances interaction between the human SUMO-conjugating enzyme…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Colorado’s Top Court Kicked Trump Off the Ballot. Will the Supreme Court Agree?</strong> - A legal scholar analyzes how the nine Justices are likely to view the blockbuster decision. - <a href="https://www.newyorker.com/news/q-and-a/colorados-top-court-kicked-trump-off-the-ballot-will-the-supreme-court-agree">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>When Americans Are the Threat at the Border</strong> - Many people charged with trafficking in Tucson are U.S. citizens, suffering from the same problems of poverty and addiction that plague the rest of the country. - <a href="https://www.newyorker.com/news/daily-comment/when-americans-are-the-threat-at-the-border">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How Netanyahu’s Right-Wing Critics See Israel’s Future</strong> - Danny Danon, the former Israeli Ambassador to the United Nations, believes there’s no path forward for a Palestinian state. - <a href="https://www.newyorker.com/news/q-and-a/how-netanyahus-right-wing-critics-see-israels-future">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An Unpermitted Shooting Range Upends Life in a Quiet Town</strong> - Residents of Pawlet, Vermont, were accustomed to calm and neighborly interactions. Then a new resident moved in. - <a href="https://www.newyorker.com/news/us-journal/one-mans-war-against-a-small-towns-rules">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Disturbing Impact of the Cyberattack at the British Library</strong> - The library has been incapacitated since October, and the effects have spread beyond researchers and book lovers. - <a href="https://www.newyorker.com/news/letter-from-the-uk/the-disturbing-impact-of-the-cyberattack-at-the-british-library">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>The best ways to help homeless people</strong> -
<figure>
<img alt="A person stands speaking to people sitting wrapped in blankets on a city sidewalk." src="https://cdn.vox-cdn.com/thumbor/m7iILug3q4inBRAI6b_u5sPH01E=/0x0:5333x4000/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72996780/1441243773.0.jpg"/>
<figcaption>
A Red Cross volunteer brings hot food and blankets to people during the night service to assist the homeless on November 13, 2022, in Catania, Italy.  | Fabrizio Villa/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
And not just at the holidays
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yLQPAc">
I’ve been covering <a href="https://www.vox.com/homelessness">America’s homeless crisis at Vox</a> all year. Last month, a reader reached out to ask what practical step they could take to help the people they see sleeping on the streets, besides giving time to food drives and occasionally handing out a drink on their walk from the store. “I often feel helpless to enact change,” the reader said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="J5pEqj">
I had some ideas but decided this was an important question to answer thoroughly, including challenging my initial assumptions about what would be most helpful. So I reached out to leading national and local experts on homelessness to get their thoughts. Their ideas represent a range of approaches, including helping individuals while working to change the system. Crucially, they encouraged doing both: Individual actions reinforce system-level change, and vice versa. A world where nobody donates blankets and socks to people experiencing homelessness is also one where political advocacy will struggle to make change.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zLFkvr">
This is a time of year when people might be especially focused on helping others and when freezing temperatures in much of the country make it particularly unsafe for people to sleep outside. But it’s not the only time of year that it’s important. Scorching temperatures can be dangerous in their own right, and the lack of affordable housing is a year-round issue.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DTRqQ2">
Here are some of the best ways to help the unhoused, and not just during the holiday season:
</p>
<h3 id="o71T9l">
<ol type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Show kindness to those living on the street
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mYliAf">
While not possible or advised in all circumstances, generally speaking, do not overlook simple and basic acts of kindness for those living without stable housing. “Look them in the eye when you walk by,” suggests Natalie Hogg, a board member and volunteer for <a href="https://www.standupforkids.org/">StandUp for Kids</a>, a youth homelessness nonprofit. “Stopping to ask how they are — being ‘seen’ and feeling like they matter means everything.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UY285o">
Some national experts, like Jesse Rabinowitz with the <a href="https://homelesslaw.org/">National Homelessness Law Center</a>, say the best thing someone could do on an individual level is to give people cash. “That enables folks to make their own choices, without red tape,” he told Vox. “People are the best experts in what they need.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lvBcan">
If you aren’t carrying cash, consider cash gift-card equivalents, like a <a href="https://www.visa.ca/en_CA/pay-with-visa/cards/gift-cards.html#:~:text=The%20Visa%20Gift%20card%20is%20a%20prepaid%20card%20welcome%20everywhere,of%20your%20friends%20and%20family.">Visa gift card</a> or a gift card that allows someone to buy food and spend time inside somewhere, like a Starbucks, McDonald’s, or Subway, so they can get warm.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="22pNWB">
Beyond giving people cash or gift cards, certain items can be particularly helpful to carry around and distribute. Donald Whitehead, the executive director of the <a href="https://nationalhomeless.org/">National Coalition for the Homeless</a>, told me he aims to do one “random act of kindness” each week and carries blankets and socks around with him to hand out. Rabinowitz, with the National Homelessness Law Center, adds that hand-warmers and hats are particularly helpful to distribute during the winter, while water and frozen water bottles are go-to needed items in the summer.
</p>
<h3 id="AgHPIb">
<ol start="2" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Donate to local shelters and nonprofits
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Gmu2fr">
Donating your resources to local shelters and nonprofits working to help those without housing is another great option. (You can use this tool from the Department of Housing and Urban Development <a href="https://www.hud.gov/findshelter">to find shelters</a> in your community.) Homeless shelters often need clothing, sleeping bags, tech equipment, backpacks, and other items. Calling them to see what they might need is a smart first step.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bI44zY">
Or consider making in-kind donations to local homeless advocacy and support groups. Hogg, with StandUp for Kids, said their chapters often need items like travel-size hygiene products, first aid items, bus passes, new and gently used clothing, office supplies, storage space, and non-perishable food.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hNIuk2">
Donating money — especially on a recurring basis — can also make a big difference. “Most don’t know that individual giving can be very important to nonprofits big and small because these gifts are unrestricted, meaning we can allocate the money wherever we see fit,” said James C. Durrah II, with <a href="https://www.miriamskitchen.org/">Miriam’s Kitchen</a>, a group working to end homelessness in Washington, DC. An “unrestricted” donation means that groups can use the money for all sorts of expenses they may have, including overhead, programming, events, and supplies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ryoW1V">
If recurring donations are not possible for your budget right now, advocates suggest considering one-time donations or donating through your workplace, where your employer might be able to match your contribution. Cassidy O’Lear, a staffer with <a href="https://familypromise.org/">Family Promise</a>, an organization focused on family homelessness, suggests launching your own fundraising campaign online, through Facebook or GoFundMe. “When you hear the word ‘fundraiser,’ images of formal dinners may come to mind,” she told Vox. “But with a virtual peer-to-peer campaign, you can bring people together to support those in need without tickets or tuxedos.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2sglYe">
Whitehead, with the National Coalition of the Homeless, stressed the value of donations, especially as of late. “We’re seeing flat funding for a lot of programs at the federal level,” he said. “Donations are down, but supporting nonprofits that can help guide people through homelessness is extremely important.”
</p>
<h3 id="bo94VI">
<ol start="3" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Volunteer
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bITTq2">
While there exist a host of opportunities to volunteer around major holidays like Thanksgiving and Christmas, many local nonprofits have programs and recurring events that rely on volunteers year-round. At Miriam’s Kitchen in DC, for example, they manage a meal program five days a week, twice a day, that is largely run by volunteers. Finding ways to fit volunteering into hectic schedules can be tough, <a href="https://www.vox.com/future-perfect/23969939/volunteering-charity-nonprofit-busy-time-remote-work-schedule-skills">but there are practical ways to do it</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VS7z1Q">
The staff who work at homeless nonprofits and shelters are typically very adept at finding ways to leverage the unique skill sets and interests of their volunteers. Maybe you’re tech-minded and can help an advocacy group improve its website. Maybe you have marketing skills or event-planning expertise. Or maybe you are interested in mentorship and the staff can connect you with homeless youth looking for guidance, support, or even academic tutoring. Getting in touch and starting a conversation is a great place to start.
</p>
<h3 id="yNiv0e">
<ol start="4" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Advocate politically<strong> </strong></li>
</ol></h3></li>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uSbUfm">
Nearly all the experts I contacted stressed the importance of using your voice to engage politically, on both the national and local levels, to help end the crisis of homelessness. That could take the form of writing to elected officials asking them to create more housing, or showing up to your local city council meeting where they’re discussing zoning to make this ask directly. Louis Chicoine, the CEO of Abode, a supportive housing organization in California, said people could also travel to the offices of their elected officials to ask why they have not done more to end homelessness, and prioritize voting for those with policy ideas dedicated to creating enough affordable housing for all Americans.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Mys22M">
If you contact a local elected official, don’t feel like you need to call with a specific policy recommendation. Making a call just to express concern about the homeless crisis and the shortage of affordable housing goes a long way, said Rabinowitz, of the National Homelessness Law Center. “Small minorities of very vocal constituents can have an outsized impact on local government,” he said. “People should be vocal on <a href="https://www.vox.com/recode/2019/5/7/18528014/fear-social-media-nextdoor-citizen-amazon-ring-neighbors">sites like Nextdoor</a> when their neighbor is saying something terrible about people experiencing homelessness. They should email their representative, comment on their Facebook page.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YUfc23">
Beyond engaging with public officials, remember that you can make a difference by educating your circle of family, friends, and coworkers. “Most people aren’t aware that every year, 2.5 million children experience homelessness in the US,” said O’Lear, with Family Promise. “You can take to social media to raise awareness.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="77qajN">
This crisis won’t be solved overnight. But there’s a lot each of us can do that would make a difference, both in the long run and right now.
</p>
<li><strong>Ferrari is an ode to dudes who love cars, from one of their own</strong> -
<figure>
<img alt="A man with white hair and sunglasses in a natty suit in front of a trailer that says “Ferrari” on the side" src="https://cdn.vox-cdn.com/thumbor/EiDnRiaXe9Gh9EhFSoBtTuhQr88=/0x0:667x500/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72995197/658098d361bd5.image.0.jpg"/>
<figcaption>
Enzo Ferrari (Adam Driver) has a lot on his mind in Michael Mann’s <em>Ferrari</em>. | Lorenzo Sisti
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Director Michael Mann loves fast cars, experts at work, and authentic filmmaking, and it shows.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="P498Sd">
Christmas Day marks the release of the 12th movie from 80-year-old director Michael Mann, <em>Ferrari</em>. Focused on a tumultuous period in the life of Enzo Ferrari (Adam Driver) in the late 1950s, the film follows the founder as he juggles two families and his failing business. The fate of his namesake company comes down to his team’s performance in the Mille Miglia, a 1,000-mile race across Italy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SVe99E">
<em>Ferrari </em>might seem like a stock prestige biopic with Academy Award aspirations; it’s a period piece that shows us an Important Person at a crossroads, split between their personal and professional lives. Driver brings back his Italian accent from <em>The House of Gucci;</em> Penélope Cruz chews the scenery as Ferrari’s wife and business partner Laura, estranged after the death of their son, Dino; Shailene Woodley plays his girlfriend Lina, with whom he has a son outside his marriage, a potential heir to the Ferrari throne.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YLp61I">
This film is a true passion project for Mann, however, who has been trying to make a Ferrari movie <a href="https://www.theguardian.com/film/2023/dec/16/michael-mann-interview-enzo-ferrari-biopic">since the 1990s</a>, his love affair with the cars dating back to the late ’60s. The director used his first big Hollywood paycheck <a href="https://www.vulture.com/2023/12/michael-mann-bought-ferrari-thief.html">on a Ferrari</a>. Mann wasn’t able to get financing <a href="https://variety.com/2023/film/global/michael-mann-ferrari-adam-driver-venice-1235705525/">until 2022</a>, and he proudly touts its independent production outside of the studio system and its distribution by Neon, the hip company responsible for bringing us films like <em>Parasite, Triangle of Sadness, </em>and <em>Anatomy of a Fall. </em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tu2k9t">
If you don’t know enough about the source material to be hyped for a movie about Enzo Ferrari, Mann in the director’s chair might well be enough of a reason to see <em>Ferrari</em>. There’s a dedicated sect of film nerds who have season tickets for anything Mann directs, from TV’s <em>Miami Vice</em> and <em>Thief</em> in the 1980s through the big screen <em>Miami Vice </em>in 2006 and his “Can you believe Thor is a hacker!?” 2015 thriller <em>Blackhat.</em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8vh5ER">
One of the hallmarks of Michael Mann’s films is that he likes stories about characters who are very good at their jobs. <em>Thief </em>features James Caan <a href="https://www.youtube.com/watch?v=SCaz3HEoU0U">painstakingly cracking safes</a> with drills and blowtorches. In <em>Heat, </em>we see Robert De Niro’s Neil McCauley <a href="https://www.youtube.com/watch?v=YBU3H3A_Q64">studying books about metals</a> to inform the planning for his <a href="https://www.youtube.com/watch?v=yT8AP0vvBL4">elaborate heists</a>. Almost every Michael Mann film features some sort of genius in their field, from FBI profilers (<em>Manhunter</em>) to dogged journalists (<em>The Insider) </em>to hackers (<em>Blackhat</em>).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rt3Mqe">
<em>Ferrari </em>is no different, with Enzo Ferrari involved in every aspect of the effort to get his cars in racing shape. Mann takes care to show Ferrari drawing blueprints of faster engines and alternately berating and inspiring his team of drivers. In Mann films, it’s rarely in doubt whether or not these experts have the skills to get the job done — it’s whether or not they can overcome their circumstances to do so, whether they’ve been dragged back to their trade for one last job or are working up the courage to make a stand against long odds.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ojhF0X">
It’s easy to be cynical about Mann’s reputation for depicting stylish, hypermasculine protagonists with emotional baggage. Enzo Ferrari more than fits the bill, looking the part in sunglasses and tailored suits while he bounces around between the two women in his life and his business is on the verge of bankruptcy. Ferrari’s drivers are all impeccably handsome and also fearless, because racing is a dangerous sport.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kXNH6h">
Because of that danger, it’s a big deal when an actor gets behind the wheel of a race car. The allure of racing fast cars has been an obsession for Hollywood actors for decades, from <a href="https://www.youtube.com/watch?v=A8T1D6Jqc3Y">Steve McQueen</a> to <a href="https://youtu.be/4Szj0gCkFuk?si=650KmUqEUibd1_-0">Paul Newman</a> to <a href="https://www.youtube.com/watch?v=fouMnwYJeQA">Rowan Atkinson</a> to reigning Sexiest Man Alive Patrick Dempsey, who is in <em>Ferrari</em> playing Italian driver Piero Taruffi (with a shock of un-McDreamy-like near-white hair). Thankfully, the racing scenes in Ferrari work, partially because <a href="https://www.youtube.com/watch?v=5E2Gi5YctUc">Dempsey does his own stunt driving</a>, actually going really, really fast.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nSutjr">
Mann has a slavish devotion to accuracy; in interviews, he proudly touts the elements of his films that are ripped from real life. For <em>Thief</em>, he hired real safecrackers as consultants, <a href="https://www.theringer.com/movies/2021/3/26/22350995/thief-michael-mann-james-caan-heist-movie">telling the Ringer</a>, “We didn’t have a props department because all we did was use all of [jewel thief] John Santucci’s work tools and his attitude.” The real-life techniques Mann portrays in <em>Blackhat </em>helped <a href="https://www.bbc.com/news/blogs-echochambers-30857751">establish its reputation</a> as one of the only films that gets hacking right. For <em>Heat, </em>Mann had the cast undergo real combat training, leading to <a href="https://www.youtube.com/watch?v=uGmT8UTPaco">a famous story</a> about footage of Val Kilmer reloading his rifle being used to train real Special Forces cadets at Fort Bragg.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="02TXQX">
In interviews for <em>Ferrari</em>, Mann often eagerly discusses the real-life details he brought to the film. In <a href="https://www.thewrap.com/ferrari-featurette-how-the-cars-were-made-michael-mann/">a featurette</a>, Mann recounts the process of recreating the period-specific Ferraris by developing 3D scans of the original vehicles and rebuilding them with modern technology. <a href="https://www.theguardian.com/film/2023/dec/16/michael-mann-interview-enzo-ferrari-biopic">Speaking to the Guardian</a>, he touts the faithful sound effects included in the film, gleefully adding, “Ferraris make a sound like no other cars. It’s music.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Cc7rfO">
The races in <em>Ferrari</em> feel real because, to a certain extent, they are. In an era where CGI is used for everything from backgrounds to faces to superhero punch-fests, the directors who can show us something legitimate are fewer and farther between. There’s a big difference between <a href="https://www.youtube.com/watch?v=228f-dPxI3Q"><em>Le Mans</em></a> and <em>The Fast and the Furious</em>, and Ferrari is buoyed by Mann’s dedication to authenticity, by the impression that there was a camera strapped to Dempsey’s car.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SWqAz7">
In modern Hollywood, the power to call your shot — figuratively and literally — is vanishing. When a director signs on to do a big-budget <a href="https://www.vox.com/marvel">Marvel</a> movie, the film comes prepackaged with a small army of CGI artists ready to paint in all the special effects. <em>Ferrari</em> was independently produced, but it wasn’t cheap. Instead, Mann designed it with care, with shots of the Italian countryside feeling as thoughtfully composed as the ones where we follow a driver moving a hundred miles per hour.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lAivMy">
The expert Mann might be most interested in is himself, as <em>Ferrari</em> doubles as a film about directing a film. In scenes where Enzo Ferrari is trying to inspire his drivers or demanding meticulous precision from his crew, it’s difficult not to think Mann’s speaking to his own experiences with actors and his below-the-line staff. It’s a hard job, being in charge, and Mann seems fascinated with Ferrari because, paraphrasing the film, he doesn’t race cars to run an automotive business — he runs a business so he can race. Mann’s films are often commercial, but <em>Ferrari </em>reminds us he makes them for the love of the art form, not just to rack up big box office numbers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eDCn1Z">
The strongest parts of <em>Ferrari</em> are imbued with Mann’s dedication to proper filmmaking. It would certainly be easier to cheat and use CGI to make it seem like Enzo Ferrari’s cars are going fast. Having the skill and the wherewithal to show us the real thing is something only a director like Michael Mann is equipped to do.
</p></li>
<li><strong>A guide to difficult conversations for people who hate confrontation</strong> -
<figure>
<img alt="A collage-style illustration of a black and white photograph of a man’s ear and back of head on the left of the frame. On the right side of the frame, a black and white photograph of a man’s mouth. Red illustrative arrows point from the mouth to the ear." src="https://cdn.vox-cdn.com/thumbor/wWZ1qYdzA3WHSaNTyngargPK9x4=/0x371:4775x3952/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72995150/GettyImages_132075562.0.jpg"/>
<figcaption>
Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“We don’t avoid conversations because they don’t matter. We avoid them because they do matter.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vYsanx">
We humans love to talk. Conversations serve many purposes: to pass the time, to learn about people and the world, to exchange information, to share a laugh. Sometimes the function of discourse is to get what we want: a change in behavior, a raise, a resolution to some disagreement. These higher-stakes conversations can be anxiety-inducing because there is so much that can go wrong. Will our partner get defensive when we ask them not to make jokes at the expense of our family? Will our best friend dismiss us when we say we fear we’ve grown apart? We may bite our tongue and hope whatever’s eating us up inside fades.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Kk6WdT">
“We don’t avoid conversations because they don’t matter,” says <a href="https://www.mikeyeomans.info/index.html">Michael Yeomans</a>, an assistant professor at Imperial College Business School who studies decision-making in conversation. “We avoid them because they do matter.”
</p>
<div class="c-float-right">
<div id="i3THTJ">
<div>
</div>
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vm42aN">
Steering clear of potentially consequential conversations can be detrimental to relationships. Left unaddressed, even minor concerns can brew into resentment, anger, and depression — often to the complete surprise of the other party. If you never have potentially thorny chats, you risk never learning the appropriate way to navigate interpersonal conflict, and those you interact with never have the opportunity to change their ways.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7yCVxk">
Hope is not lost. There are tactics you can employ to deftly share your concerns without accusation, embarrassment, or outrage. All that’s needed is a plan, an objective outlook, and an understanding of what your conversation partner will be most receptive to.
</p>
<h3 id="pMdvoj">
What to do before you have the conversation
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="adn3v6">
Before bringing up a gripe or potential point of contention, decide if it’s even worth discussing. Are you just in a bad mood and are likely to feel differently tomorrow? Is the issue something that you’re unable to change and may only ruffle feathers? (Like telling your partner you find their parents annoying.) Take a beat and consider the alternatives to the discussion, suggests <a href="https://www.missouristate.edu/cmjf/profile-display.aspx?p=erinwehrman">Erin Wehrman</a>, an associate professor at Missouri State University whose research focuses on interpersonal and family communication. What’s the best possible outcome from broaching this conversation? What’s the worst? If the worst that could happen is you argue for a few minutes, you may consider bringing up your concerns.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xqFpRh">
Taking time to reflect may allow you to be more objective in assessing the situation. Try to focus on the facts of the situation, Wehrman says, instead of filling in the blanks and assuming the other person’s intentions. Your cousin made a comment and it made you angry. A neighbor parked in front of your house and you felt disrespected. “My story about why people do the things that they do,” Wehrman says, “that is my story, that’s opinion.” Collecting and presenting the facts gives your conversation partner the opportunity to explain their perspective without needing to go on the defensive.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GBcowZ">
You may be feeling nervous about angering or disappointing the person you want to speak to — “this is normal, and emotions are very normal,” Wehrman says. “It’s just part of our body’s reaction to stress.” She suggests preparing exactly what you’ll say and then considering a few potential ways the other person might respond. Have a plan for each outcome. If they respond to your concerns defensively, you might take a different approach (more on this later) than if they are validating and receptive. Remind yourself that improving a relationship involves advocating for yourself.
</p>
<h3 id="wrCBug">
How to prepare for the conversation
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1BywWu">
If you decide the issue is worth discussing, you’ll want a plan based on your goals. What do you hope to accomplish? Then consider how the other person might react based on different ways of broaching the conversation. You want to avoid venting, for instance, if you’d like the other person to change their behavior in some way, like becoming more mindful of the language they’re using in front of your children. “Try to avoid using them as a listening board for your own emotions because that translates to very different goals,” says <a href="https://profiles.arizona.edu/person/segrin">Chris Segrin</a>, head of the University of Arizona’s department of communication and a behavioral scientist whose specialty is interpersonal relationships. “I want to get this off my chest, off my mind, versus there’s something I would like to see different, some change.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WzjS37">
Think about the setting, too. You won’t want to initiate a deep conversation at the dinner table with extended family or after they’ve worked a 16-hour shift, says licensed marriage and family therapist <a href="https://kiaundrajackson.com/">Kiaundra Jackson</a>. “If they are in a good mood, if they’re smiling, if they just ate,” she says, “this might be a good time to have that difficult conversation.” Just be sure to ask if they’re open to chatting before interrupting their favorite TV show.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RRtQZR">
Then make a plan for when you’ll walk away. If anyone starts yelling or name-calling, you’ll suggest taking a breather and revisiting the conversation later, Wehrman says.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BJNByd">
Segrin suggests rehearsing what you’ll say ahead of time, either mentally or with a trusted neutral party.
</p>
<h3 id="HJNsV3">
How to start the conversation
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RZkVWx">
Getting the ball rolling can be the most stressful part of any difficult conversation. Be sure to use “I” statements. Telling someone they’ve done something wrong puts the blame on them — and they’ll likely get defensive, Segrin says.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ATw8fd">
If you’re at a loss, here are some expert-approved statements to help initiate the conversation:
</p>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sk3nU0">
<em>I see you’re eating dinner right now, but I wanted to talk to you about something. Is now a good time? </em>
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xIj74R">
<em>Ever since we hung out last week, I haven’t stopped thinking about that comment you made about [X]. I wanted to talk to you about that because it’s been bothering me.</em>
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VaYifW">
<em>Sorry I haven’t brought this up before, but I’d really like to talk about [X]. </em>
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mo5ZiF">
<em>I’ve noticed you [react a certain way] when I [do something]. From my perspective, it seems like…</em>
</li>
</ul>
<h3 id="iiFBI8">
Skills to use to make sure the conversation runs smoothly
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qB8qKc">
There are many trust-building and relationship-strengthening strategies to employ even in the most difficult conversations, Yeomans says. Simply being receptive to the other person’s concerns promotes a culture of respect instead of aggression. “I’m always shocked when people don’t realize that when they are aggressive in a disagreement that other people respond with aggressiveness,” Yeomans says. “If you start off nice, people will take that cue from you.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OZ5bU9">
To signal receptiveness and promote productive conversations, Yeomans has developed a “receptiveness recipe.” Strategies include actively acknowledging the other person’s perspective, highlighting areas where you both agree, softening your claims by using language like “I think…” or “I see it this way…,” using positive statements such as “I think it’s helpful when…” instead of “You shouldn’t be doing this,” and sharing personal stories. Even when you disagree with a sibling’s view on how to care for your parents, it’s crucial to demonstrate you’ve actually listened to their argument (“I understand where you’re coming from”; “I see your point”), addressed common concerns (“I do agree that Mom needs extra support”), and avoided being too forceful when suggesting alternatives (“I think it would be helpful to find a part-time home aid; I’ve heard from friends in similar situations that their parents still had independence, but assistance when needed”). These tactics can be particularly helpful to have in your back pocket if a loved one approaches <em>you</em> with a thorny conversation you weren’t prepared for.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sxvk3c">
Don’t expect to persuade your conversation partner to totally see things your way. Instead, aim to learn more about how your loved one feels or views the situation and vice versa, Yeomans says. “I want to understand your perspective” or “I want to understand where you’re coming from” is more constructive than trying to strong-arm someone into changing their mind completely.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o7PwEe">
Continually check in with yourself and the other person throughout the discussion to weigh whether everyone feels comfortable continuing, Jackson says. Ask if they want to take a break or revisit at another time. If things are getting heated, suggest stepping away for a few minutes to get some air or picking up the conversation again in a few days.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="v0aw8B">
Again, think about the conditions for when you’ll walk away from a combative person. If a line is crossed, you can say, “I can tell this is important to you, but I don’t really want to continue to talk about this right now.”
</p>
<h3 id="85LptQ">
How to wrap up a difficult conversation
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iUazs4">
If the conversation reaches a point of resolution, first confirm with whomever you’re talking with that they, too, feel satisfied. “Never assume that you have an agreement with them,” Segrin says. Try asking, “Would you agree that tomorrow you’ll bring waste bags on your walk with your dog?” or “How comfortable are you with the plan to not discuss personal details about our relationship with friends anymore?” Give them the space to express their takeaways from the conversation. “Too many people have failed to wrap these up by just assuming <em>I said my piece, everything’s going to magically fix itself</em> — not really,” Segrin says. “Ask them explicitly, ‘Do you feel like we have come to an agreement about how this might change in the future and how comfortable you are with that?’ See if you’re going to get a buy-in from them.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UpTgF0">
Show your appreciation for your conversation partner by thanking them for taking your concerns seriously, even if you didn’t come to an agreement, Wehrman says. (You can say, “I know we don’t see eye-to-eye on this, but I appreciate you letting me have a turn to talk.”)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="c6pAgG">
Always remain focused on the future, Segrin says. Blame is retroactive and does nothing to change what already occurred. “If you want change, that’s a future orientation,” Segrin says. “So keep it on the future and don’t get carried away with pointing fingers about who’s responsible for what happened in the past.”
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phenom, Bubbly Boy, and Dash catch the eye</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>El Asesino, Ascoval, Bruce Almighty, Measure Of Time, and Crime Of Passion shine</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Want to achieve what nobody has achieved in South Africa: Rohit Sharma</strong> - Rohit Sharma also did not want to speak about his cricketing future, just saying that he wants to enjoy the game.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IND vs SA first Test | Rohit’s men gear up to end 31-year wait for series win in South Africa</strong> - The two-match Test rubber, starting in Centurion on the Boxing Day, will be India’s ninth away series in the Rainbow Nation since 1992</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>FIFA threatens to suspend Brazil over confederation president’s removal by court</strong> - FIFA has warned Brazil it could suspend its national teams and clubs from international competitions if an intervention at its soccer body leads to the election of a new president in January</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Kerala to tap beach tourism potential fully</strong> - Tourism Minister opens floating bridge at Varkala Papanasam Beach</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Here are the big stories from Karnataka today</strong> - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated and written by Nalme Nachiyar.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PM Modi releases book on collected works of Madan Mohan Malaviya</strong> - The bilingual (English and Hindi) work in 11 volumes, spread across about 4,000 pages, is a collection of the writings and speeches of Malaviya</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>HC directive to provide necessary assistance to pilgrims stranded on their way to Sabarimala</strong> - The court had earlier issued various directions to ensure that there is proper crowd management at Sannidhanam, Pamba and Nilakkal and also along the trekking path from Pamba to Sannidhanam.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Army chief Gen. Manoj Pande exhorts commanders to conduct operations in ‘most professional manner’</strong> - The Chief of Army Staff (CoAS) also asked them to remain resolute and steadfast against all challenges.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Serbia protests: Anti-government demonstrators try to storm Belgrade city hall</strong> - The opposition demands a re-run of last week’s elections won by the ruling party, claiming mass fraud.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine celebrates first Christmas on 25 December</strong> - The move to the Western calendar is seen as a further shift away from Moscow’s influence.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Man dies after Dublin restaurant shooting</strong> - A man in his 40s has been shot and a second man is also seriously injured.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Slovakia arrest over threat to copy Prague attack</strong> - The suspect said he wanted to repeat Thursday’s shooting in neighbouring Czech Republic, police say.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cologne Cathedral: Extra checks at German landmark after attack warning</strong> - German police are deployed near the cathedral, amid fears of attacks in several European countries.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Corvids seem to handle temporary memories the way we do</strong> - Birds show evidence that they lump temporary memories into categories. - <a href="https://arstechnica.com/?p=1992736">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PAX Unplugged 2023: How indie devs build and sell new board games</strong> - Tabletop is bigger than ever. What’s it like trying to get your game out there? - <a href="https://arstechnica.com/?p=1992547">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Matter, set to fix smart home standards in 2023, stumbled in the real market</strong> - Gadget makers, unsurprisingly, are hesitant to compete purely on device quality. - <a href="https://arstechnica.com/?p=1992230">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>US agency tasked with curbing risks of AI lacks funding to do the job</strong> - Lawmakers fear the NIST will have to rely on companies developing the technology. - <a href="https://arstechnica.com/?p=1992640">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>People exaggerate the consequences of saying no to invites</strong> - People are more understanding of the reasons for rejections than most of us think. - <a href="https://arstechnica.com/?p=1992723">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Putin is woken up by one of his generals.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The general says, “Vladimir Vladimirovich, the Ukrainians want to talk about surrender.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Putin replies, “Sure! Get Zelensky on the phone with me.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The general asks, “What phone? They’re right here!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/MudakMudakov"> /u/MudakMudakov </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/18qatos/putin_is_woken_up_by_one_of_his_generals/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/18qatos/putin_is_woken_up_by_one_of_his_generals/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A vagina is the greatest engine on the planet.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
It gets turned on just by a finger.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
It self lubricates.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
It changes its own oil every 4 weeks.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/1HotCanadian"> /u/1HotCanadian </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/18q7cru/a_vagina_is_the_greatest_engine_on_the_planet/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/18q7cru/a_vagina_is_the_greatest_engine_on_the_planet/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man in a bar, after several drinks, began bragging that he could identify any type of wood by its smell only. The patrons of the bar decided to test him. The man was blindfolded and presented with several pieces of wood.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
First they tried maple. He smelled it and said, “That’s maple.” They then tried ebony; he again smelled it and named the wood correctly. He did this with every piece of wood they brought before him. The bartender then got an idea to trick him. And they took one of the waitresses and put her crotch up to his nose. He sniffed for a while. “Boy,” he said “This is difficult. Flip that board over and let me smell the other side.” So they took they waitress and put her ass near his nose. He took a big whiff, started to smile and said, “You guys can’t fool me! That’s the shit house door from a tuna boat!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/YZXFILE"> /u/YZXFILE </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/18qfqcl/a_man_in_a_bar_after_several_drinks_began/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/18qfqcl/a_man_in_a_bar_after_several_drinks_began/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I wish my husband would treat me like his penis.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I would get oily massages every morning.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He would be taking pretty pictures of me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I would be the one making all of his decisions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He would only beat me twice a week.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/1HotCanadian"> /u/1HotCanadian </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/18q7aok/i_wish_my_husband_would_treat_me_like_his_penis/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/18q7aok/i_wish_my_husband_would_treat_me_like_his_penis/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>If Die Hard is a Christmas movie, then this has to be a Christmas joke.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I was on a train the other day when two Swedish men sat down next to me The two introduced themselves as Sven and Olf. Olf in particular was wearing a t-shirt with the USSR flag on and boasted a cap with a hammer and sickle on, so I assumed he was an avid communist. I asked them if either of them knew where I could get alcohol on the train, and Olf piped up:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“If you go to carriage 4, you can get a Guinness, you idiot. You can also find a Stella in carriage 6, dumbass. There’s also someone microbrewing in the front of the train, but he looks stupid.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I was a bit taken aback at how mean Olf was, but I thanked him for the information. Soon after, when he got up to go to the bathroom, I asked Sven what the deal was with his friend.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Don’t worry” he said. “Rude Olf the red knows train beer.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Make_the_music_stop"> /u/Make_the_music_stop </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/18pur3v/if_die_hard_is_a_christmas_movie_then_this_has_to/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/18pur3v/if_die_hard_is_a_christmas_movie_then_this_has_to/">[comments]</a></span></p></li>
</ul>
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